Investigation of gastrointestinal tumor symptoms and risk factors in eighty patients with Parkinson’s disease

Abstract

BACKGROUND

Parkinson’s disease (PD) is often accompanied by gastrointestinal symptoms; however, the relationship between PD and gastrointestinal tumors remains unclear.

AIM

To explore the symptom characteristics and risk factors of gastrointestinal tumors in patients with PD by integrating clinical, neurological, gastrointestinal, and laboratory assessments.

METHODS

Eighty patients with PD who were admitted to our hospital between January 2023 and December 2024 were retrospectively analyzed. Clinical characteristics and neurological status were evaluated using standardized scales, including the Mini-Mental State Examination, Depression Anxiety Stress Scale-21, Pittsburgh Sleep Quality Index Barthel Index, Non-Motor Symptoms Scale, and the Intake, Feeling nauseated, Emesis, physical Exam, Duration of symptoms (I-FEED) gastrointestinal dysfunction score. Laboratory indicators including tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 72-4 (CA72-4)] were measured. Differences between PD patients with and without gastrointestinal tumors were compared, and logistic regression was used to identify associated factors.

RESULTS

Among the 80 PD patients, 16 (20.00%) had gastrointestinal tumors. The most common symptoms in the tumor group were constipation (93.75%), urgency of defecation (75.00%), and abdominal tightness (75.00%). Patients with gastrointestinal tumors had significantly higher I-FEED, CEA, CA19-9, and CA72-4 levels (P < 0.05). Logistic regression revealed that sex, disease duration, I-FEED score, and the levels of CEA, CA19-9, and CA72-4 were independently associated with the presence of gastrointestinal tumors, while Non-Motor Symptoms Scale was not significantly related.

CONCLUSION

This study uniquely combines neurological symptom scales and tumor markers to evaluate gastrointestinal tumor risk in patients with PD. The findings suggest that gastrointestinal dysfunction and tumor marker elevation are key clinical indicators, and highlight the importance of comprehensive assessment in identifying high-risk PD patients for timely intervention.

Key Words: Parkinson’s disease; Gastrointestinal tumors; Symptom characteristics; Risk factors; Clinic

Core Tip: This study investigated 80 patients diagnosed with Parkinson’s disease and revealed that approximately 20% of them had coexisting gastrointestinal tumors. Common symptoms included constipation and urgent bowel movements. The presence of tumors was significantly associated with factors such as sex, disease duration, gastrointestinal function scores, and elevated levels of multiple tumor markers, offering insight into early identification of high-risk patients.

INTRODUCTION

Parkinson’s disease (PD) is a neurodegenerative disease of the nervous system, which mostly occurs in the older population[1]. The incidence of gastrointestinal symptoms is relatively high in the current clinical diagnosis and treatment of patients with PD. It has been found that the incidence of gastrointestinal symptoms is also relatively high[2]. A key feature of the pathological manifestations of PD is the aggregation of α-synuclein in the brain, which then forms Lewy bodies. According to existing research, abnormal aggregation of α-synuclein may also occur in nerve cells of the gastrointestinal tract. This aggregation may start in the gastrointestinal tract and spread to the brain through nerve pathways, such as the tenth cranial nerve, thus playing a role in the pathogenesis of PD[3]. Therefore, in this experiment, a comprehensive evaluation was carried out on 80 patients with PD admitted to our hospital who had symptoms of gastrointestinal tumors in order to deeply explore the symptom characteristics and related risk factors of gastrointestinal tumors in the development process of PD.

MATERIALS AND METHODS

General data

Eighty patients with PD who were admitted to our hospital between January 2023 and December 2024 were selected.

Inclusion criteria: (1) Meeting the diagnosis of PD[4]; (2) Complete clinical data; and (3) Informed consent.

Exclusion criteria: (1) Infectious diseases; (2) Taking drugs that affect gastrointestinal function in the past 3 months; (3) Having mental diseases; (4) Malignant lesions in other organs; and (5) Digestive system diseases.

Methods

Collection of general information: Clinical data: General information included patients’ names, sex, age, and educational background.

Cognitive function assessment: The Mini-Mental State Examination has a total of 30 items with a total score of 30 points[5].

Depression Anxiety Stress Scale-21 score: This scale consists of 3 subscales with a total of 21 items, with each item scored from 0 point to 3 points. Higher scores indicate more severe depression, anxiety, and stress[6].

Pittsburgh Sleep Quality Index: The Pittsburgh Sleep Quality Index was used to evaluate the sleep status of the two groups of patients. The total score was 21 points, and sleep quality was inversely proportional to this score[7].

Activities of daily living: The Barthel Index has a total of 10 items and 100 points. The ability to perform activities of daily living was directly proportional to the score[8].

Assessment of non-motor symptoms: The Non-Motor Symptoms Scale (NMSS)[9], consisting of 30 items, was used, with a total score ranging from 30 points to 360 points. Symptom severity is directly proportional to the score.

Gastrointestinal function: Intake, Feeling nauseated, Emesis, physical Exam, Duration of symptoms (I-FEED), which evaluates intake, feelings of nausea, emesis, physical examination findings, and duration of symptoms, was used to assess gastrointestinal function[10], with a total score ranging from 0 point to 15 points.

Detection of laboratory indicators: The Erythrocyte Sedimentation Rate (ESR) reflects the inflammatory state. Triglyceride, total cholesterol, high-density lipoprotein cholesterol/Low-density lipoprotein cholesterol related to lipid metabolism, carbohydrate antigen 72-4 (CA72-4), carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA) have reference values for tumor diagnosis.

Statistical analysis

The data collected in this experiment were analyzed using the software SPSS 23.0. Measurement data are described as mean ± SD, and the t-test is used to compare the differences between groups; Count data are described as, n (%) and analyzed by the χ² test. Statistical significance was set at P < 0.05 difference.

RESULTS

General situation

Among the 80 enrolled patients with PD, there were 36 males and 44 females; the age was 39-79 (64.28 ± 8.47) years old; the disease course was 0.5-10 (3.15 ± 1.48) years; educational background: 63 patients had a junior high school education or below, and 17 patients had a high school education or above, and the BMI was 23.51 ± 1.66 kg/m².

Symptoms of gastrointestinal tumors in patients with PD

Of the 80 patients, 16 (20.00%) had PD with gastrointestinal tumors and 64 (80.00%) had PD without gastrointestinal tumors. Constipation (93.75%), bowel urgency (75.00%), and abdominal tightness (75.00%) were the most common symptoms in this study. The clinical characteristics of the patients are presented in Table 1.

Table 1 Symptoms of gastrointestinal tumors in patients with Parkinson’s disease.

Symptom	n (%)
Constipation	15 (93.75)
Abdominal bloating	10 (62.50)
Incomplete defecation	11 (68.75)
Weight loss	2 (12.50)
Heartburn	1 (6.25)
Abdominal pain	8 (50.00)
Nausea and vomiting	7 (43.75)
Dysphagia	3 (18.75)
Urgent defecation	12 (75.00)
Abdominal cramping	12 (75.00)
Increased flatulence	9 (56.25)
Hematochezia	6 (37.50)

Factor analysis associated with PD with gastrointestinal tumor symptoms

Comparison of general data: Patients with PD and those with PD without sex or course (P < 0.05), with no differences in other general data (P > 0.05), as shown in Table 2.

Table 2 Comparison of two groups, mean ± SD.

Characteristic	PD with gastrointestinal tumor (n = 16)	PD without gastrointestinal tumor (n = 64)	t/χ² value	P value
Gender (male), n (%)	12 (75.00)	24 (37.50)	5.836	0.016
Age (years)	63.48 ± 4.51	64.51 ± 3.98	0.902	0.370
Onset age (years)	61.32 ± 3.59	61.49 ± 3.67	0.166	0.868
Disease duration	3.69 ± 1.24	1.13 ± 0.29	15.189	< 0.001
Education level			0.044	0.834
Junior high school or below, n (%)	13 (81.25)	51 (79.69)
High school or above, n (%)	3 (18.75)	13 (20.31)
BMI (kg/m²)	23.44 ± 1.13	23.26 ± 1.45	0.462	0.645

PD: Parkinson’s disease; BMI: Body mass index.

Scale and data comparison: Patients with PD and gastrointestinal tumors showed significant differences in NMSS and I-FEED scores compared to those without PD (P < 0.05), while no significant differences were observed in other scales (P > 0.05), as shown in Table 3.

Table 3 Comparison of data of two groups of scales, mean ± SD.

Characteristic	PD with gastrointestinal tumours (n = 16)	The PD was not accompanied by gastrointestinal tumors (n = 64)	t/χ2	P value
MMSE	15.33 ± 1.48	15.64 ± 1.33	0.815	0.417
DASS-21	37.81 ± 2.08	38.02 ± 2.14	0.353	0.725
PSQI	18.42 ± 1.26	18.21 ± 1.33	0.571	0.570
BI	31.16 ± 2.43	30.97 ± 2.24	0.298	0.766
NMSS	60.51 ± 3.29	43.59 ± 3.99	15.661	< 0.001
I-FEED	10.49 ± 1.56	4.65 ± 1.11	17.273	< 0.001

PD: Parkinson’s disease; MMSE: Mini-Mental State Examination; DASS-21: Depression Anxiety Stress Scale-21; PSQI: Pittsburgh Sleep Quality Index; BI: Barthel Index; NMSS: Non-Motor Symptoms Scale; I-FEED: Intake, Feeling nauseated, Emesis, physical Exam, Duration of symptoms.

Comparison of laboratory indicators: Patients with PD with gastrointestinal tumors and patients with PD without gastrointestinal tumors had differences in CEA, CA19-9, and CA72-4 Levels (P < 0.05) and no differences in other indicators (P > 0.05), as shown in Table 4.

Table 4 Comparison of laboratory indicators of the two groups, mean ± SD.

Characteristic	PD with gastrointestinal tumours (n = 16)	The PD was not accompanied by gastrointestinal tumors (n = 64)	t/χ2	P value
CEA (ng/mL)	7.33 ± 0.48	4.34 ± 0.33	29.414	< 0.001
CA19-9 (U/mL)	39.86 ± 2.08	28.01 ± 2.34	18.495	< 0.001
CA72-4 (U/mL)	8.31 ± 1.15	5.12 ± 0.44	17.809	< 0.001
TG (mmol/L)	0.98 ± 0.13	1.04 ± 0.24	0.962	0.339
TC (mmol/L)	4.31 ± 0.29	4.33 ± 0.19	0.336	0.738
HDL-C (mmol/L)	1.49 ± 0.16	1.45 ± 0.11	1.180	0.241
LDL-C (mmol/L)	2.38 ± 0.23	2.44 ± 0.13	1.391	0.168
ESR (mmol/L)	12.26 ± 1.34	12.34 ± 1.22	0.230	0.819

PD: Parkinson’s disease; CEA: Carcinoembryonic antigen; CA19-9: Carbohydrate antigen 19-9; CA72-4: Carbohydrate antigen 72-4; TG: Triglyceride; TC: Total cholesterol; HDL-C: High-density lipoprotein cholesterol; LDL-C: Low-density lipoprotein cholesterol; ESR: Erythrocyte sedimentation rate.

Logistic regression analysis of PD with gastrointestinal tumor symptoms

Patients with PD and gastrointestinal tumors were related to patient sex, disease duration, I-FEED score, and CEA, CA19-9, and CA72-4 Levels (P < 0.05), as detailed in Table 5.

Table 5 Logistic regression analysis.

Group	β	SE	Wald	P value	OR (95%CI)
Gender	2.366	0.258	84.282	< 0.001	10.654 (6.429-17.656)
Course of disease	0.753	0.379	3.956	0.047	2.124 (1.011-4.462)
NMSS	0.082	0.101	0.659	0.417	1.085 (0.891-1.321)
I-FEED	0.885	0.337	6.900	0.009	2.424 (1.252-4.693)
CEA	0.578	0.204	7.997	0.005	1.782 (1.194-2.660)
CA19-9	0.641	0.236	7.370	0.007	1.898 (1.195-3.015)
CA72-4	0.583	0.285	4.174	0.041	1.791 (1.024-3.133)

OR: Odds ratio; CI: Confidence interval; NMSS: Non-Motor Symptoms Scale; I-FEED: Intake, Feeling nauseated, Emesis, physical Exam, Duration of symptoms; CEA: Carcinoembryonic antigen; CA19-9: Carbohydrate antigen 19-9; CA72-4: Carbohydrate antigen 72-4.

DISCUSSION

PD is a neurodegenerative disease with diverse clinical manifestations. The core symptoms include two major categories: Motor and non-motor symptoms. Non-motor symptoms are characterized by a large variety of symptoms, a wide range of involvement, and a high incidence rate[11]. The importance of gastrointestinal symptoms in PD has become increasingly evident in current clinical research. Constipation is the most common gastrointestinal symptom of PD, and some patients may experience it in the early stages of the disease. The gastrointestinal symptoms caused by PD can affect the entire digestive tract, often leading to various adverse physiological reactions such as indigestion, nausea, and vomiting[12]. Gastrointestinal symptoms may be indicative of gastrointestinal tumors. When symptoms do not resolve persistently, progress progressively, or are accompanied by other alarming symptoms, the risk of gastrointestinal tumors increases significantly. However, there is currently a lack of comprehensive assessment of gastrointestinal tumor symptoms in patients with PD in China, and the factors influencing these symptoms remain to be clarified. Therefore, through a comprehensive and systematic assessment and management of gastrointestinal tumor symptoms in this study, we aimed to deeply explore the symptom characteristics and related risk factors of gastrointestinal tumors in the development of PD.

The results showed that constipation (93.75%), urgency of defecation (75.00%), and abdominal tightness (75.00%) were the most common. Reason analysis: Weakened gastrointestinal motility caused by PD and changes in the intestinal structure and inflammatory response caused by gastrointestinal tumors are superimposed, greatly exacerbating the degree of gastrointestinal dysfunction. The intestine, which already has slow peristalsis owing to PD, is even more difficult to excrete under the influence of a tumor, and the symptoms of constipation become more severe. Moreover, this severe gastrointestinal dysfunction further stimulates the intestine, causing symptoms such as urgency of defecation and abdominal tightness[13]. In addition, the neuropathy caused by PD may affect the innervation of the tumor microenvironment and change the growth and invasion characteristics of tumor cells. Similarly, gastrointestinal tumors and the inflammation they cause may further interfere with nerve function abnormalities related to PD through the nerve conduction pathway, forming a vicious cycle that leads to the appearance of adverse gastrointestinal symptoms[14].

The results of this study showed that there were differences in sex and disease course between patients with PD with and without gastrointestinal tumors (P < 0.05), and there were no differences in other general data (P > 0.05). However, it should be noted that the temporal relationship between the onset of PD and the development of gastrointestinal tumors remains unclear. Specifically, it is unknown whether gastrointestinal tumors existed prior to the diagnosis of PD or subsequently developed. Future research should explore this temporal relationship through longitudinal studies or detailed medical history reviews to better understand the pathophysiological mechanisms underlying the association between PD and gastrointestinal tumors. This may be attributed to differences in hormone levels between males and females. Estrogen has a protective effect on the gastrointestinal mucosa. However, hormones such as androgens may play a role in promoting the occurrence and development of tumors in men. In the pathological environment of PD, hormonal imbalance may be further exacerbated, affecting the proliferation and differentiation of gastrointestinal cells[15].

The results of this experiment showed that there were differences in the NMSS and I-FEED scores between patients with PD with and without gastrointestinal tumors (P < 0.05), and there were no differences in other scales (P > 0.05). Reason analysis: Pain and digestive dysfunction caused by gastrointestinal tumors can cause patients to experience more fatigue, sleep disorders, and mental symptoms, resulting in their scores being significantly higher than those of patients with PD without gastrointestinal tumors[16]. Gastrointestinal tumors and the inflammatory reactions they cause may also affect the function of peripheral nerves and the autonomic nervous system. This dual influence on nerve function is more significant in patients with PD and gastrointestinal tumors, leading to the exacerbation of a series of non-motor symptoms. Gastrointestinal tumor growth directly damages the normal structure and function of the gastrointestinal tract. The tumor may block the intestine, affecting the passage of food, digestion, and absorption, leading to symptoms such as difficulty eating, nausea, and vomiting, all of which increase the I-FEED score[17]. In addition, PD can cause gastrointestinal function problems, such as insufficient gastrointestinal motility and abnormal secretion of digestive juices. When combined with gastrointestinal tumors, the effects of these two diseases on the gastrointestinal tract are superimposed[18].

The results of this experiment showed that there were differences in CEA, CA19-9, and CA72-4 Levels between patients with PD with and without gastrointestinal tumors (P < 0.05), and no differences were observed in other indicators (P > 0.05). It should be emphasized that CEA and CA19-9 have low specificity in gastrointestinal tumors. Elevated levels of these markers can also be observed in various inflammatory conditions and other non-tumor-related diseases. Therefore, the use of these markers alone for the diagnosis of gastrointestinal tumors in patients with PD should be approached with caution. Further diagnostic evaluations, such as imaging studies or histopathological examinations, are essential to confirm the presence of gastrointestinal tumors. Reason analysis: CEA, CA19-9, and CA72-4 are commonly used tumor markers in clinical practice[19]. In patients with PD with gastrointestinal tumors, owing to the presence of tumor lesions, tumor cells continuously secrete these markers, resulting in significantly higher concentrations of these markers in the blood than in patients with PD without gastrointestinal tumors. Triglyceride, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol mainly reflect lipid metabolism[20]. In patients with PD, these indicators are easily affected by various factors, such as diet, medications, and basal metabolism, and have little correlation with the presence or absence of gastrointestinal tumors. ESR, a nonspecific inflammatory indicator, changes when an inflammatory response is triggered by gastrointestinal tumors[21]. However, in this study, owing to the presence of a certain inflammatory state in PD itself and the fact that the gastrointestinal tumor may be in a relatively early stage and has not yet caused an obvious systemic inflammatory response, the ESR did not show a significant difference between the two groups of patients.

However, it should be noted that the temporal relationship between the onset of PD and the development of gastrointestinal tumors remains unclear. Specifically, it is unknown whether the gastrointestinal tumors existed prior to the diagnosis of PD or developed subsequently. Future research should explore this temporal relationship through longitudinal studies or detailed medical history reviews to better understand the pathophysiological mechanisms underlying the association between PD and gastrointestinal tumors. It should be emphasized that CEA and CA19-9 have low specificity in gastrointestinal tumors. Elevated levels of these markers can also be observed in various inflammatory conditions or other non-tumor-related diseases. Therefore, the use of these markers alone for diagnosing gastrointestinal tumors in PD patients should be approached with caution. Further diagnostic evaluations, such as imaging studies or histopathological examinations, are essential to confirm the presence of gastrointestinal tumors.

This study has several limitations. First, it was conducted at a single center with a relatively small sample size, which may limit the generalizability of the findings. Second, the retrospective design restricts the ability to draw causal inferences between PD and gastrointestinal tumors. Third, the potential confounding effects of antiparkinsonian medications, such as levodopa, on gastrointestinal function were not controlled for, which may have influenced symptom presentation and biomarker levels. Future prospective, multicenter studies with larger cohorts and more comprehensive medication data are needed to validate these findings.

CONCLUSION

In conclusion, this study investigated 80 patients with PD and found that symptoms such as constipation and urgency of defecation in patients with PD and gastrointestinal tumors are relatively common. Sex, disease course, I-FEED score, and CEA, CA19-9, and CA72-4 Levels are related to the occurrence of gastrointestinal tumors. However, although NMSS scores were higher in the tumor group, logistic regression analysis indicated that NMSS was not significantly associated with the presence of gastrointestinal tumors (P = 0.417). Therefore, its role as an independent risk factor is not supported by this study. These findings provide a basis for understanding the relationship between PD and gastrointestinal tumors, help identify high-risk patients early, and improve the management and prognosis of patients with PD.